JP5905833B2 - 心筋虚血−再潅流障害の予防、処置または遅延のための、ニューレグリンを含む組成物およびその利用 - Google Patents
心筋虚血−再潅流障害の予防、処置または遅延のための、ニューレグリンを含む組成物およびその利用 Download PDFInfo
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Description
本発明は、哺乳動物、特にヒトの虚血−再潅流障害の予防、処置または遅延のための薬剤の調製におけるニューレグリンの使用に関する。とりわけ、本発明は、虚血−再潅流傷害の予防、処置または遅延のための、ニューレグリンを含む組成物およびニューレグリンを利用する方法に関する。
血管の浚渫または虚血後の血管再開通術は、血液の再潅流を目的としており、たいていの事例において好ましい治療効果が得られる。しかしながら、特定の条件下においては、より深刻な結果となる。虚血再潅流障害(IRI)は、臨床試験において見られるばかりでなく、相違する種の動物研究(例えば、ウサギ、ラット、テンジクネズミ、イヌ、およびブタ等)においても確かめられている。
A.発明の概要
本発明は、NRGが、心臓血管の発生および成体の通常の心臓機能の維持に不可欠であるという発見に基づいている。また、NRGは、心筋細胞の分化、筋節および細胞骨格構造の組織化、ならびに細胞接着を増強する。本発明はまた、心不全の数種の異なる動物モデルにおいて、NRGが心筋作用の悪化を有意に改善するか、この悪化から有意に防御すし、心不全動物の生存を長引かせ、中大脳動脈閉塞再潅流の動物モデルでは大脳細胞を防御するという発見に基づいている。ニューレグリン、ニューレグリンポリペプチド、ニューレグリン誘導体、またはニューレグリンの活性を模倣している化合物は、本発明の範囲に含まれる。
B.定義
他に定義の無い限り、本明細書において用いられている全ての技術的用語および科学的用語は、本発明が属する分野の当業者に一般的に理解されている意味と同じ意味を有している。本明細書において言及されている全ての特許、出願、公開された出願、および他の刊行物は、その全体が参照として本明細書に組み込まれる。この項目で説明されている定義が、本明細書に参照として組み込まれている特許、出願、公開された出願、および他の刊行物に説明された定義に反する場合、または矛盾する場合には、この項目において説明されている定義が、参照として本明細書に組み込まれている定義よりも優先する。
図1:ラットの心臓の切片におけるTCC染色の結果である。切片における白い区域(TCC非染色)は、梗塞形成区域である。文字「A」、「B」、「C」および「D」は、それぞれグループA、グループB、グループCおよびグループDを表している。
本発明は、以下に続く非限定的な実施例を参照することにより、さらに例証されるだろう。この実施例は、本発明をどのように製造し、どのように用いるかの完全な開示および説明を当業者に提供するために出されるものであり、以下の試験が実施した全てまたは唯一の試験であることを示すことを意図するものではない。
試験薬剤および試験物質:
rhNRG−1:Zensun (Shanghai) Science & Technology Ltdによって製造。配列番号1のアミノ酸を有する。バッチナンバー:200503007;各バイアル250μg(5000U)のrhNRG−1。
プラセボ:Zensun (Shanghai) Science & Technology Ltdによって製造された、rhNRG−1のビヒクル。バッチナンバー:200503001F。
rhThymosin−β4:Northland (Beijing) Bio-Technology Co Ltdによって製造。バッチナンバー:20050728。
Claims (24)
- ヒト患者において心筋虚血再潅流障害を予防する、または遅延させるための組成物を製造するための、NRG−1タンパク質の使用であって、上記組成物は、有効量のNRG−1タンパク質を含み、上記NRG−1タンパク質は、上記ヒト患者における心筋梗塞の大きさを止める、または低減する、使用。
- 上記NRG−1タンパク質は、NRG−1のEGF様ドメインを含んでいる、請求項1に記載の使用。
- 上記NRG−1タンパク質は、配列番号1で表されるアミノ酸配列を含んでいる、請求項1に記載の使用。
- 上記心筋虚血再潅流障害は、冠動脈バイパス移植手術、冠動脈血管形成術、臓器移植手術、血栓溶解療法または心肺バイパス手術などの治療的介入の結果生じたものである、請求項1に記載の使用。
- 上記組成物は、虚血再潅流障害用の予防薬または治療薬と組み合わせて用いられる、請求項1に記載の使用。
- 上記予防薬または治療薬は、フリーラジカル捕捉物質、免疫抑制物質および虚血性組織の代謝を向上させる薬剤から選択される、請求項5に記載の使用。
- 上記フリーラジカル捕捉物質は、外因性SOD、アロプリノール、ビタミンE、ビタミンC、カタラーゼ、またはジメチルスルホキシド(DMSO)である、請求項6に記載の使用。
- 上記免疫抑制物質は、シクロスポリンA、タクロリムス、ミコフェノール酸モフェチル、バシリキシマブ、ダクリズマブ、ムロモナブ、または副腎皮質ステロイドである、請求項6に記載の使用。
- 虚血性組織の代謝を向上させる上記薬剤は、解糖基質−リン酸ヘキソース、外因性ATP、ヒドロキノン、またはチトクロムCである、請求項6に記載の使用。
- ヒト患者における心筋虚血再潅流障害の予防、または遅延用の組成物であって、上記組成物は、NRG−1タンパク質の有効量を含み、上記NRG−1タンパク質は、上記ヒト患者における心筋梗塞の大きさを止める、または低減する、組成物。
- 上記NRG−1タンパク質は、NRG−1のEGF様ドメインを含んでいる、請求項10に記載の組成物。
- 上記NRG−1タンパク質は、配列番号1で表されるアミノ酸配列と一致している、請求項10に記載の組成物。
- 上記心筋虚血再潅流障害は、冠動脈バイパス移植手術、冠動脈血管形成術、臓器移植手術、血栓溶解療法または心肺バイパス手術などの治療的介入の結果生じたものである、請求項10に記載の組成物。
- ヒト患者において心筋虚血再潅流障害を予防する、または遅延させるための組合せ物であって、上記組合せ物は、請求項10に記載の組成物と、心筋虚血再潅流障害を予防する、または遅延させるための予防薬または治療薬の有効量とを含み、上記組合せ物は、上記ヒト患者における心筋梗塞の大きさを止める、または低減する、組合せ物。
- 上記予防薬または治療薬は、フリーラジカル捕捉物質、免疫抑制物質および虚血性組織の代謝を向上させる薬剤から選択される、請求項14に記載の組合せ物。
- 上記フリーラジカル捕捉物質は、外因性SOD、アロプリノール、ビタミンE、ビタミンC、カタラーゼ、またはジメチルスルホキシド(DMSO)である、請求項15に記載の組合せ物。
- 上記免疫抑制物質は、シクロスポリンA、タクロリムス、ミコフェノール酸モフェチル、バシリキシマブ、ダクリズマブ、ムロモナブ、または副腎皮質ステロイドである、請求項15に記載の組合せ物。
- 虚血性組織の代謝を向上させる上記薬剤は、解糖基質−リン酸ヘキソース、外因性ATP、ヒドロキノン、またはチトクロムCである、請求項15に記載の組合せ物。
- 上記心筋梗塞の大きさを、少なくとも10%まで低減する、請求項14に記載の組合せ物。
- 上記心筋梗塞の大きさを、少なくとも20%まで低減する、請求項14に記載の組合せ物。
- 上記心筋梗塞の大きさを、少なくとも10%まで低減する、請求項1に記載の使用。
- 上記心筋梗塞の大きさを、少なくとも20%まで低減する、請求項1に記載の使用。
- 上記心筋梗塞の大きさを、少なくとも10%まで低減する、請求項10に記載の組成物。
- 上記心筋梗塞の大きさを、少なくとも20%まで低減する、請求項10に記載の組成物。
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EP3363455A1 (en) | 2005-12-30 | 2018-08-22 | Zensun (Shanghai) Science & Technology, Co., Ltd. | Extended release of neuregulin for improved cardiac function |
JP6096262B2 (ja) | 2009-08-25 | 2017-03-15 | ゼンサン (シャンハイ) サイエンス アンド テクノロジー,シーオー.,エルティーディー. | ニューレグリンに基づく心不全の治療方法 |
CN102139095A (zh) | 2010-01-29 | 2011-08-03 | 上海泽生科技开发有限公司 | 神经调节蛋白用于预防、治疗或延迟心脏缺血再灌注损伤的方法和组合物 |
WO2013053076A1 (en) | 2011-10-10 | 2013-04-18 | Zensun (Shanghai)Science & Technology Limited | Compositions and methods for treating heart failure |
WO2013082458A1 (en) | 2011-12-02 | 2013-06-06 | The Regents Of The University Of California | Reperfusion protection solution and uses thereof |
CA2884051A1 (en) | 2012-10-08 | 2014-04-17 | Zensun (Shanghai) Science & Technology, Ltd. | Compositions and methods for treating heart failure in diabetic patients |
EP3610905B1 (en) | 2013-05-22 | 2021-03-31 | Zensun (Shanghai) Science & Technology, Co., Ltd. | Extended release of neuregulin for treating heart failure |
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CN102139095A (zh) | 2010-01-29 | 2011-08-03 | 上海泽生科技开发有限公司 | 神经调节蛋白用于预防、治疗或延迟心脏缺血再灌注损伤的方法和组合物 |
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